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The Helicase Aquarius/EMB-4 Is Required to Overcome Intronic Barriers to Allow Nuclear RNAi Pathways to Heritably Silence Transcription

The Helicase Aquarius/EMB-4 Is Required to Overcome Intronic Barriers to Allow Nuclear RNAi Pathways to Heritably Silence Transcription

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Authors

  • Alper Akay
  • Tomas Di Domenico
  • Kin M. Suen
  • Amena Nabih
  • Guillermo E. Parada
  • Mark Larance
  • Ragini Medhi
  • Ahmet C. Berkyurek
  • Xinlian Zhang
  • Christopher J. Wedeles
  • Konrad L.M. Rudolph
  • Jan Engelhardt
  • Martin Hemberg
  • Ping Ma
  • Angus I. Lamond
  • Julie M. Claycomb
  • Eric A. Miska (Lead / Corresponding author)

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Original languageEnglish
Pages (from-to)241-255.e6
Number of pages21
JournalDevelopmental Cell
Volume42
Issue number3
Early online date7 Aug 2017
DOIs
StatePublished - 7 Aug 2017

Abstract

Small RNAs play a crucial role in genome defense against transposable elements and guide Argonaute proteins to nascent RNA transcripts to induce co-transcriptional gene silencing. However, the molecular basis of this process remains unknown. Here, we identify the conserved RNA helicase Aquarius/EMB-4 as a direct and essential link between small RNA pathways and the transcriptional machinery in Caenorhabditis elegans. Aquarius physically interacts with the germline Argonaute HRDE-1. Aquarius is required to initiate small-RNA-induced heritable gene silencing. HRDE-1 and Aquarius silence overlapping sets of genes and transposable elements. Surprisingly, removal of introns from a target gene abolishes the requirement for Aquarius, but not HRDE-1, for small RNA-dependent gene silencing. We conclude that Aquarius allows small RNA pathways to compete for access to nascent transcripts undergoing co-transcriptional splicing in order to detect and silence transposable elements. Thus, Aquarius and HRDE-1 act as gatekeepers coordinating gene expression and genome defense.

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    ©2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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